David B. Drown

Pulmonary clearance of soluble and insoluble forms of manganese

Manganese is an essential metal of toxicologic concern primarily because of exposure via inhalation. Environmental forms of Mn exist mainly as insoluble oxides, yet much of the research information available relates to the soluble salts. In the present study, adult male Sprague-Dawley rats were intratracheally instilled with either soluble MnCl2 or insoluble Mn3O4 labeled with 54Mn. Lungs and other major organs were sampled over a span of 3 mo after dosing with the respective chemicals, which were equivalent to 8 mu Ci and 1 mumol of manganese in 0.2 ml of buffer. There was rapid clearance of Mn from the lungs in the case of both chemicals; the chloride cleared at an initial rate of nearly four times that of the oxide. Despite this early difference, the amount of 54Mn remaining in the lungs after 2 wk was similar for both compounds. The level of 54Mn in the liver, kidney, spleen, and testes peaked at the 3-d sampling point in the case of the oxide, whereas the chloride peaked in these organs within 4 h. At 1 wk after administration, however, the 54Mn activity was comparable for both compounds in most organs sampled. Mn uptake in the brain was also more rapid with the chloride form, but both compounds remained at high levels for several weeks.

Persistence of Vanadium Compounds in Lungs after Intratracheal Instillation in Rats

Translocation and tissue distribution of two different forms of vana dium compounds, orthovanadate (soluble) and vanadium pentox ide (less soluble), were investigated. Groups of randomly selected rats were injected intratracheally with radiolabeled vanadium (48V) compounds and the animals were sacrificed at 1, 7 and 28 days after treatment. Blood, lungs and other major organs and tissues, namely liver, kidney, spleen, heart, testes, brain, muscle, and bone were sampled and the vanadium contents determined by gamma spectrometry. The less soluble form of vanadium (vanadium pent oxide) was eliminated from the lungs at a slow but exponentially linear rate, whereas the soluble form was translocated rapidly from this organ and exhibited a non-linear decline. Compared to the less soluble form, significantly less vanadium was retained in lungs 7 and 28 days after intratracheal instillation of vanadate. One day after treatment significantly higher concentrations (approximately 4 times) of vanadium after orthovanadate were observed in liver, kidney, spleen and bone compared to the pentoxide. However, tissue residues at 7 and 28 days indicated that both forms of vanadi um were rapidly eliminated, except from bone and lungs. Results suggest a prolonged retention of less soluble forms of vanadium and possible health effects following repeated occupational expo sure.

Effects of Repeated Intermittent Exposures to Nitrous Oxide on Central Neurotransmitters and Hepatic Methionine Synthetase Activity in Cd-1 Mice

The central neurotransmitters and hepatic methionine synthetase (MS) appear to play an important role in mediating the side effects associated with N2O exposure. Male CD-1 mice were exposed to 0, 50, 500, and 5,000 ppm of N2O 6 hr per day, 5 days a week for 2 or 13 weeks. One day after the last day of exposure, the animals were decapitated and steady state concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT), 3-methoxy-4-hydroxy- mandelic acid (VMA), 3-methoxy-4-hydroxyphenyl glycol (MOPEG), dihydroxyphenylacetic acid (DOPAC), and 5-hydrox yindoleacetic acid (5-HIAA) were determined in six discreet brain regions using electrochemical high-performance liquid chromatogra phy. Hepatic MS activity was measured using a newly developed non-isotopic method. After a 2-week exposure to 5,000 ppm N2O, levels of NE and DA in some brain regions were significantly increased and were accompanied by significant decreases in the levels of their major metabolites. Serotonin levels were significantly decreased in certain brain regions. After the 13-week exposure to

Effects of benzo[a]pyrene on steady-state levels of biogenic amines and metabolizing enzymes in mouse brain regions

Benzo[a]pyrene (BaP) is a product of incomplete fossil fuel combustion, a well-known pollutant, and a carcinogenic agent. In the present study male CD-1 mice received ip injections of 0, 5, 25, and 100 mg/kg body weight BaP twice a week for 3 weeks. Endogenous levels of brain biogenic amines and their selected metabolites, norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), vanillylmandelic acid, dihydroxyphenylacetic acid (DOPAC), homovanillic acid, and 5-hydroxyindoleacetic acid (5-HIAA) were measured using high performance liquid chromatography and electrochemical detection. The brain regions studied were cortex, striatum, hypothalamus, midbrain, medulla oblongata, and cerebellum. BaP treatment increased the steady-state levels of NE, DA, and 5-HT in the hypothalamus and striatum. Increased levels of DA and 5-HT and their major metabolites DOPAC and 5-HIAA were noticed in the same region, an indication of increased metabolism of these amines. The increase in the 5-HT level in the cortex was not dose-related. Levels of NE and DA were significantly higher in the medulla oblongata. There was a concurrent increase in activities of tyrosine hydroxylase and tryptophan hydroxylase in several brain regions. The effect of BaP on Dopa-decarboxylase was not consistent. Monoamine oxidase was occasionally inhibited. Results indicate that exposure to BaP altered the steady-state levels of biogenic amines in various brain regions and these changes were consistent with the activities of metabolizing enzymes.

Tolerance to cadmium and cadmium-binding ligands in Great Salt Lake brine shrimp (Artemia salina)

Information on the accumulation of cadmium in cytosolic proteins of Great Lake brine shrimp (Artemia salina) was obtained from animals collected directly from the lake and also from animal hatched and maintained in three sublethal concentrations of cadmium (0.5, 2.0, 5.0 ppm) in saltwater aquaria. Brine shrimp growth under these conditions was monitored by measuring body lengths during a 7-day exposure period. Heat-stable, cadmium-binding ligands were isolated and identified by Sephadex G-75 chromatography and atomic absorption spectrophotometry. Cadmium was found to be equally distributed between high and low molecular weight proteins in animals collected from the lake and the 0.5 ppm cadmium group. There was also a slight growth stimulation noted in the 0.5-pm group. Higher cadmium incorporation was noted in low molecular weight fractions with increasing cadmium concentration in the exposure media. Low molecular weight fractions were also found to have high uv absorption characteristics at 250 nm and low absorption at 280 nm. Molecular weight of the cadmium-binding ligands was found to be 11,000 as estimated by the gel filtration method. De novo synthesis of this protein was increased as a function of cadmium concentration in the media. However, slow accumulation of cadmium in other protein fractions was also noticed in higher cadmium exposure groups, suggesting the existence of possible tolerance mechanisms in brine shrimp exposed to suspected acute cadmium concentrations.

Detection of Resin Acid Compounds in Airborne Particulate Generated from Rosin Used as a Soldering Flux

Various uses of rosin and exposure to its resin acid constituents have been associated with dermal and pulmonary sensitization. Methodology is presented to detect resin acids common to rosin (such as abietic and dehydroabietic acid) found in aerosol from heated rosin flux. Air filtration, solvent filter extraction, and gas chromatography/mass spectrometry were used to provide qualitative and quantitative information on the resin acid content of aerosol produced during soldering with rosin flux. Abietic acid and dehydroabietic acid were identified and quantified in aerosol derived from heated rosin flux, in samples collected in the field and in laboratory generated samples. Other resin acids (including several apparently oxidized resin acids) were detected, but not quantified. Laboratory mass balance experiments using soldering temperatures and liquid rosin flux showed that much of the nonvolatile material originally present in unheated flux may be captured on a sampling filter following heating and aerosolization. The data presented suggest that resin acids are a major component (with regard to mass) of the airborne contaminants produced during soldering with rosin flux. Abietic acid was shown to be unstable on sampling filters held for a period of weeks, while dehydroabietic acid and total solvent-soluble material were not found to degrade under the same conditions. Rosin aerosol produced in the laboratory using a soldering iron and liquid rosin flux produced particles shown to be of respirable size using scanning electron microscopy.

Effects of Phosphorus Enrichment and Wave Simulation on Populations of Ulothrix Zonata from Northern Lake Superior

The effects of phosphorus enrichment and wave simulation on new (denuded rocks) and established populations of Ulothrix zonata were examined in specially designed stationary and rocking tanks on a bedrock ledge overlooking the western arm of Lake Superior at Castle Danger, Minnesota. Tanks received constant flow of lake water and were exposed to the same insolation and climatic conditions as the lake for a 10-week period during July, August, and September 1972. A rocking tank and a stationary tank were enriched to maintain an average concentration of 0.16 mg/L PO4–P. Two remaining tanks, receiving only lake water, served as controls. Each week, algal material was harvested from the tanks and analyzed for chlorophyll a, ash-free dry weight, and abundance of U. zonata and associated non-filamentous periphytic algae. Diatoms comprised, on the average, 95% of the total non-filamentous periphytic algae. The results show that phosphorus enrichment has marked effects on established populations of U. zonata in addition to favoring recolonization of U. zonata on bare rock substrates. Statistical analysis of the data revealed that phosphorus enrichment caused a significant increase in Ulothrix biomass and chlorophyll a in the enriched tanks. Wave simulation caused a significant reduction in total numbers of non-filamentous algae associated with Ulothrix in the rocking tanks.

A stationary cold vapor method for atomic absorption measurement of mercury in blood and urine used for exposure screening

A method is provided for rapid, accurate flameless atomic absorption Hg determinations in blood and urine used for exposure screening of mercury. Instead of the conventional apparatus requiring separate reduction and absorption containers, a one-piece reduction-absorption cell was fitted on the burner mount of an atomic absorption spectrophotometer. A five mL aliquot of the digested urine or blood sample was pipetted into the cell and one mL reductant added. The background corrected absorbance was recorded after three minutes of mixing. Heating the absorption cell at 60°C eliminated the formation of water vapor on the quartz windows of the tube. Sensitivity of the method was 1.0 ng which corresponds to a concentration of 0.2 ng/mL using a 5 mL sample size. The accuracy of Hg determinations in human blood and urine was confirmed by the method of standard additions of Hg to undigested samples. In order to test the applicability of the method to biological samples from Hg exposed individuals, rats were injec...

Oxidized resin acids in aerosol derived from rosin core solder.

Exposure to rosin during a variety of uses has been associated with dermal and pulmonary sensitization. Oxidized resin acids are present in many rosin products, and have been regarded as the main sensitizing rosin compounds in cases of dermal sensitization. This research describes oxidized resin acids identified in aerosol produced during soldering with rosin core solder. Oxidized resin acids found were 7-oxodehydroabietic acid, 15-hydroxydehydroabietic acid, and 7-hydroxydehydroabietic acid. The presence of oxidized compounds known to be dermal sensitizers in aerosol from rosin flux soldering supports the hypothesis that resin acid compounds are pulmonary sensitizers as previously proposed. Changes in the composition of resin acid aerosol derived from heated rosin core solder (compared with the parent material) are described.

A Nose-Only Inhalation Exposure System for Generation, Treatment and Characterization of Formaldehyde Vapor

A description of a novel symmetrical nose-only inhalation chamber for small animals is presented. The chamber utilizes a circular design and a round baffle plate around which the test atmosphere is evenly drawn in order to expose each symmetrically placed animal port to equivalent gas concentrations without exposing animals to each others expired gases. The nose-only mode may be more suitable for inhalation exposures as compared to whole-body exposures which allow skin contamination and possible aerosol ingestion through preening habits. Evidence is presented that nose-only exposure which requires animal restraint is no more stressful than freely-caged exposure as measured by total peripheral white blood cell counts and the ease of animal entry into the restraining tubes. Applications of the exposure system are described for the case of pure formaldehyde vapor generation. The method of formaldehyde generation entails heating solid paraformaldehyde polymer in a mineral oil bath and diluting with filtered ...